Engineering Bacteroides thetaiotaomicron to produce non-native butyrate based on a genome-scale metabolic model-guided design = 게놈 규모의 대사모델 설계 기반의 부티레이트 생산 박테로이데스 균주 엔지니어링

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Title
Engineering Bacteroides thetaiotaomicron to produce non-native butyrate based on a genome-scale metabolic model-guided design = 게놈 규모의 대사모델 설계 기반의 부티레이트 생산 박테로이데스 균주 엔지니어링
Author(s)
K Kim; D Choe; Y Song; M Kang; Seung Goo LeeDae Hee Lee; B K Cho
Bibliographic Citation
Metabolic Engineering, vol. 68, pp. 174-186
Publication Year
2021
Abstract
Bacteroides thetaiotaomicron represents a major symbiont of the human gut microbiome that is increasingly viewed as a promising candidate strain for microbial therapeutics. Here, we engineer B. thetaiotaomicron for heterologous production of non-native butyrate as a proof-of-concept biochemical at therapeutically relevant concentrations. Since B. thetaiotaomicron is not a natural producer of butyrate, we heterologously expressed a butyrate biosynthetic pathway in the strain, which led to the production of butyrate at the final concentration of 12 mg/L in a rich medium. Further optimization of butyrate production was achieved by a round of metabolic engineering guided by an expanded genome-scale metabolic model (GEM) of B. thetaiotaomicron. The in silico knock-out simulation of the expanded model showed that pta and ldhD were the potent knock-out targets to enhance butyrate production. The maximum titer and specific productivity of butyrate in the pta-ldhD double knockout mutant increased by nearly 3.4 and 4.8 folds, respectively. To our knowledge, this is the first engineering attempt that enabled butyrate production from a non-butyrate producing commensal B. thetaiotaomicron. The study also highlights that B. thetaiotaomicron can serve as an effective strain for live microbial therapeutics in human.
Keyword
Bacteroides thetaiotaomicronGenome-scale metabolic modelFlux-balance analysisButyrateCommensal microbes
ISSN
1096-7176
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ymben.2021.10.005
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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